Around most small cancers there is an area where microscopic sized cancers cells have spread out or migrated. Normally a surgeon tries to remove the tumor with a rim of normal tissue so that he is sure of removing these small cells as well. If cancer cells are found right up to the edge of the resected tissue, this is referred to as having cancer at the margin (or positive margins). Cancer patients have a reduced chance of cancer recurrence if resection margins are negative. Current techniques to assess surgical margins involve post-operative evaluation of pathology specimens collected during surgery. If the pathology specimen is positive, additional surgery may be required. Therefore, a method to intraoperative assess the resection margin prior to actual resection will minimize the chance of a positive microscopic margin and minimize the need for additional surgery.
In addition, determining the presence or absence of axillary lymph nodal metastasis is critical to the pathologic staging, prognostication and guidance of treatment in patients with certain cancers, such as breast cancer (Stacker, S. A., et al. Nat Rev Cancer 2:573-583 (2002); Tafreshi, N. K., et al. Cancer Control 17:143-155 (2010)). The sentinel lymph node (SLN) is the axillary node that first receives drainage from the breast parenchyma in the area of the primary tumor and, therefore has the highest probability of containing metastatic cells. SLNs can be identified by a surgical application referred to as intraoperative lymphatic mapping (ILM or SLN mapping). ILM helps trace the lymphatic drainage patterns in a cancer patient to evaluate potential tumor drainage and cancer spread in lymphatic tissue. The ILM technique does not detect cancer; rather it helps surgeons identify the lymph node(s) to which a tumor is likely to drain and spread. ILM involves peritumoral injection of a radioactive tracing agent to identify SLNs, which are then biopsied for pathological examination (Albertini, J. J., et al. JAMA 276:1818-1822 (1996); Giuliano, A. E. et al. Annals of Surgery 220:391-401 (1994); Krag, D. N. et al. Surg Oncol 2:335-340 (1993)). The sulfer colloid of technetium 99m (99mTc) is a radioactive tracing agent particularly suited for ILM. Moreover, the radioactive tracing agent Lymphoseek® (Tilmanocept) described in U.S. Pat. No. 6,409,990 is designed to accumulate in lymphatic tissue by specifically binding to mannose binding receptor (MBR; CD206) proteins that reside on the surface of resident dendritic cells and macrophages. If biopsied SLNs are negative for cancer, then complete axillary lymph node dissection can be avoided (Douglas-Jones, A. G. et al. Histopathology 55:107-113 (2009)).
However, a limitation of ILM techniques is the lack of biomarkers for targeting these agents to cancer cells. Instead, such agents distribute non-specifically across SLNs providing only an anatomic and non-functional map (Galanzha, E. I. et al. J Biophotonics 2:528-539 (2009); McElroy, M. et al. J Surg Res 151:68-73 (2009)). As a result, SLN biopsy is required to identify potential cancer cells. SLN biopsy is an invasive surgical procedure, requiring a multidisciplinary team with specialized imaging and surgical equipment (Douglas-Jones, A. G. et al. Histopathology 55:107-113 (2009); Krag, D. et al. N Engl J Med 339:941-946 (1998); McMasters, K. M. et al. J Clin Oncol 18:2560-2566 (2000); Ung, O. A. et al. Asian J Surg 27:284-290 (2004)), and may have postoperative complications, such as lymphedema, seroma formation, sensory nerve injury, and limitation in range of motion (Purushotham, A. D. et al. J Clin Oncol 23:4312-4321 (2005)). The majority of breast cancer patients (74%) who undergo SLN biopsy are pathologically negative (Krag, D. N. et al. Lancet Oncol 8:881-888 (2007)). Moreover, biopsies fail to identify axillary disease in 5-10% of patients (McMasters, K. M. et al. J Clin Oncol 18:2560-2566 (2000); Ung, O. A. et al. Asian J Surg 27:284-290 (2004)). Therefore, a non-invasive method for detecting cancer with improved sensitivity and specificity and eliminating unnecessary surgeries is warranted.
It is an object of the invention to provide compositions and methods for non-invasive detection of cancer in a subject.
It is a particular object of the invention to provide compositions and methods for in vivo molecular imaging of cancer cells, such as metastatic cancer cells and pancreatic cancer cells, in a subject.
It is a further object of the invention to provide compositions and methods for label-guided surgery for cancer.
It is a particular object of the invention to provide compositions and methods for label-guided surgery for pancreatic cancer.
It is a further object of the invention to provide cell-surface markers that can be used to detect cancer cells in vivo.
It is a particular object of the invention to provide cell-surface markers that can be used to detect pancreatic cancer cells in vivo.